Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions

Autor: Robert Keehan, Roberta Goodall, Oliver Beaumont, Akihiro Nishiguchi, Lizeth Lacharme-Lora, Michele Giugliano, Michiya Matsusaki, Christopher Coyle, Hiroyoshi Y. Tanaka, Tracey Masters, Nicki Cohen, Jon Hanley, Veronica H.L. Leinster, C. Patrick Case, Andrew D. Randall, Kristian Aquilina, Ian L. Sargent, Katja Simon, Nagaraj D. Halemani, Jennifer McGarvey, William Ind, Helena Kemp, Simon Grant, Emma Scull-Brown, Sharan Athwal, Aman Sood, Daniel J Curtis, Mitsuru Akashi, Rocco A Barone, Jon D. Lane, Thomas E. Phillips, Gavin Collett, Mitsunobu R. Kano, Leila Cornes, Xun Liu, Marianne Thoresen, Dionne Tannetta
Rok vydání: 2014
Předmět:
Placenta
Dendrite
Settore BIO/09 - Fisiologia
Membrane Potentials
Tissue Culture Techniques
0302 clinical medicine
Pregnancy
Hypoxia
Cells
Cultured

Parvalbumin
Cerebral Cortex
Neurons
0303 health sciences
GABAA receptor
Glutamate receptor
Cerebral cortex
Development
Neurodevelopmental disorder
Neurone
Reoxygenation
Schizophrenia
Brain
Cell Hypoxia
medicine.anatomical_structure
Neurology
embryonic structures
Female
medicine.symptom
medicine.medical_specialty
Biology
03 medical and health sciences
Fetus
Developmental Neuroscience
Internal medicine
Glial Fibrillary Acidic Protein
medicine
Animals
Humans
Rats
Wistar

030304 developmental biology
Cytotrophoblast
Dose-Response Relationship
Drug

Dendrites
Hypoxia (medical)
Embryo
Mammalian

Rats
Oxygen
Endocrinology
Animals
Newborn

Culture Media
Conditioned

Human medicine
Reactive Oxygen Species
030217 neurology & neurosurgery
Immunostaining
Zdroj: Experimental neurology
ISSN: 0014-4886
Popis: Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during fetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and fetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytototrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca2 +]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers in vitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions.
Databáze: OpenAIRE